» Articles » PMID: 37233155

Transcriptomic Comparison of Human Peripartum and Dilated Cardiomyopathy Identifies Differences in Key Disease Pathways

Abstract

Peripartum cardiomyopathy (PPCM) is a rare form of acute onset heart failure that presents in otherwise healthy pregnant women around the time of delivery. While most of these women respond to early intervention, about 20% progress to end-stage heart failure that symptomatically resembles dilated cardiomyopathy (DCM). In this study, we examined two independent RNAseq datasets from the left ventricle of end-stage PPCM patients and compared gene expression profiles to female DCM and non-failing donors. Differential gene expression, enrichment analysis and cellular deconvolution were performed to identify key processes in disease pathology. PPCM and DCM display similar enrichment in metabolic pathways and extracellular matrix remodeling suggesting these are similar processes across end-stage systolic heart failure. Genes involved in golgi vesicles biogenesis and budding were enriched in PPCM left ventricles compared to healthy donors but were not found in DCM. Furthermore, changes in immune cell populations are evident in PPCM but to a lesser extent compared to DCM, where the latter is associated with pronounced pro-inflammatory and cytotoxic T cell activity. This study reveals several pathways that are common to end-stage heart failure but also identifies potential targets of disease that may be unique to PPCM and DCM.

Citing Articles

The molecular and cellular landscape of hypertrophic cardiomyopathy phenotypes: transition from obstructive to end-stage heart failure.

Taylor J, Lal S, Braet F, McLachlan C, Li A J Mol Med (Berl). 2025; 103(1):113-123.

PMID: 39774683 DOI: 10.1007/s00109-024-02508-7.


Pharmacological interventions for peripartum cardiomyopathy.

Papapanou M, Vaidakis D, Paraskevas T, Sergentanis T, Siristatidis C Cochrane Database Syst Rev. 2024; 10:CD014851.

PMID: 39474978 PMC: 11523253. DOI: 10.1002/14651858.CD014851.

References
1.
Halliday B, Wassall R, Lota A, Khalique Z, Gregson J, Newsome S . Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial. Lancet. 2018; 393(10166):61-73. PMC: 6319251. DOI: 10.1016/S0140-6736(18)32484-X. View

2.
Papa S, Choy P, Bubici C . The ERK and JNK pathways in the regulation of metabolic reprogramming. Oncogene. 2018; 38(13):2223-2240. PMC: 6398583. DOI: 10.1038/s41388-018-0582-8. View

3.
Takeuchi A, Badr M, Miyauchi K, Ishihara C, Onishi R, Guo Z . CRTAM determines the CD4+ cytotoxic T lymphocyte lineage. J Exp Med. 2015; 213(1):123-38. PMC: 4710199. DOI: 10.1084/jem.20150519. View

4.
Koenig A, Shchukina I, Amrute J, Andhey P, Zaitsev K, Lai L . Single-cell transcriptomics reveals cell-type-specific diversification in human heart failure. Nat Cardiovasc Res. 2022; 1(3):263-280. PMC: 9364913. DOI: 10.1038/s44161-022-00028-6. View

5.
Goli R, Li J, Brandimarto J, Levine L, Riis V, McAfee Q . Genetic and Phenotypic Landscape of Peripartum Cardiomyopathy. Circulation. 2021; 143(19):1852-1862. PMC: 8113098. DOI: 10.1161/CIRCULATIONAHA.120.052395. View